Ozone-induced nasal hyperresponsiveness to tachykinins in guinea pigs.
OBJECTIVE
To assess role of hydroxyl radials in the ozone-induced upper airway hyper-responsiveness to tachykinins.


METHODS
A prospective, controlled, animal model (n = 96) was performed. Half of them exposed to air (A-group, placebo) and the other half exposed to 3 ppm ozone (O-group) for 2 h. Two hours post air/ozone exposure, animals were anesthetized and equally randomized to be pretreated with one of the three treatments, including saline vehicle, dimethylthiourea (DMTU; 500 mg/kg m, a hydroxyl radical scavenger), or phosphoramidon (Phos; 2 mg/kg, an inhibitor for neutral endopeptidase). Ten minutes after pretreatment, half of the animals in each group were i.v. injected with capsaicin (2 microg/kg), and the other half were i.v. injected with substance P (10 microg/kg) to produce Evans blue dye extravasation.


RESULTS
Nasal exudative response to capsaicin or substance P in O-group was found to be significantly greater than that in A-group. This ozone-induced nasal airway hyperresponsiveness was largely prevented by DMTU. Phosphoramidon produced a similar nasal airway hyperresponsiveness in the A-group, but failed to alter ozone-induced nasal airway hyperresponsiveness in O-group. In sharp contrast, only substance P, but not capsaicin, produced a laryngeal exudative response in the A-group, which was similar to that in the O-group. The laryngeal exudative response to substance P was not significantly affected by DMTU or Phos.


CONCLUSIONS
In the guinea-pig model, hydroxyl radicals play a vital role in the development of ozone-induced nasal airway hyperresponsiveness to tachykinins. It is possibly mediated through the suppressive action of ozone on the tachykinin degradation.
Ho
Ching-Yin
CY
Department of Otolaryngology, Veterans General Hospital-Taipei and National Yang-Ming University, Taipei, Taiwan. cyho@vghtpe.gov.tw
Tan
Ching-Ting
CT
Tsai
Hung-Huey
HH
Kou
Yu Ru
YR
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D004195:Disease Models, Animal; D005122:Exudates and Transudates; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D010083:Oxidants, Photochemical / Q000633:toxicity; D010126:Ozone / Q000633:toxicity; D011446:Prospective Studies; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D018689:Sensory System Agents / Q000008:administration & dosage; D013373:Substance P / Q000008:administration & dosage*; D015320:Tachykinins / Q000008:administration & dosage; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D016166:Free Radical Scavengers; D018377:Neurotransmitter Agents; D010083:Oxidants, Photochemical; D018689:Sensory System Agents; D015320:Tachykinins; D013373:Substance P; D010126:Ozone; C038983:1,3-dimethylthiourea; D013890:Thiourea; D002211:Capsaicin